Phytolaccin, which, in the literature, has been referred to as PAP--Phytolacca americana protein--is a plant-derived proteinaceous toxin which inhibits protein biosynthesis. The biological properties of various plant toxins was a subject reviewed by Olsnes, S., and Pihl, A., in Receptors and Recognition Series B: The Specificity and Action of Animal, Bacterial and Plant Toxins, Cuatrecasas, ed., pp. 130-173, (Chapman and Hall, London, 1976). Phytolaccin has been found to demonstrate antiviral activity in plants, Duggar, B. M., and Armstrong, J. K., Ann. Missouri Bot. Garden, Vol. 12, pp. 359-366 (1925); Grogan, R. G., and Kimble, K. A., Phytopathology, Vol. 54, pp. 75-78 (1964).
The protein was first purified from Phytolacca sp. by Wyatt and Shepherd, see Phytopathology, Vol. 59, pp. 1787-1794 (1969) and subsequently, two forms of the protein were isolated and were determined to exhibit similar biological activities, Irvin, J. D., Arch. Biochem. Biophys., Vol. 169, pp. 522-528 (1975); Irvin, J. D., Kelley, T. and Robertus, J. D. Arch Biochem. Biophys., Vol. 200, pp. 418-425 (1980).
Phytolaccin was the first of the plant-derived toxins shown to be a potent inhibitor of protein biosynthesis in eukaryotic cell-free systems, Obrig, T. G., Irvin, J. D., and Hardesty, B., Arch. Biochem. Biophys., Vol 155, pp. 278-289 (1973). At that time, it was concluded that inhibition appeared to involve a specific effect of the agent on the larger (60S) ribosomal subunit. Moreover, it was shown that maximum inhibition of protein synthesis occurred at a 1:10 molar ratio of inhibitor to ribosomes, suggesting that phytolaccin possessed enzymatic properties. The inhibitory action of phytolaccin was demonstrated to be directly on the ribosome, resulting in an altered functional interaction of ribosomes with elongation factors EF-1 and EF-2 . The nature of the ribosomal lesion caused by phytolaccin, however, remains to be elucidated.
To date, purification of phytolaccin from plants has been carried out by conventional methods of ion-exchange chromatography.
Herpes viruses are eukaryotic, DNA viruses. Known anti-herpetic agents include pharmaceuticals such as Acyclovir (Burroughs-Wellcome Co.) and Arildone (Sterling Drug Co.). The long-term effectiveness of these agents is in question, as clinical observations have indicated that the target virus can develop resistance to the drugs shortly after initiation of therapy.